Swarts, B. M., Holsclaw, C. M., Jewett, J. C., Alber, M., Fox, D. M., Siegrist, M. S., Leary, J. A., Kalscheuer, R., & Bertozzi, C. R. (2012). Probing the mycobacterial trehalome with bioorthogonal chemistry. Journal of the American Chemical Society, 134(39), 16123-16126.
PMID: 22978752;PMCID: PMC3466019;Abstract:
Mycobacteria, including the pathogen Mycobacterium tuberculosis, use the non-mammalian disaccharide trehalose as a precursor for essential cell-wall glycolipids and other metabolites. Here we describe a strategy for exploiting trehalose metabolic pathways to label glycolipids in mycobacteria with azide-modified trehalose (TreAz) analogues. Subsequent bioorthogonal ligation with alkyne-functionalized probes enabled detection and visualization of cell-surface glycolipids. Characterization of the metabolic fates of four TreAz analogues revealed unique labeling routes that can be harnessed for pathway-targeted investigation of the mycobacterial trehalome. © 2012 American Chemical Society.
He, J., Kimani, F. W., & Jewett, J. C. (2017). Rapid in Situ Generation of Benzene Diazonium Ions under Basic Aqueous Conditions from Bench-Stable Triazabutadienes. SYNLETT, 28(14), 1767-1770.
Moncarz, J. R., Brunker, T. J., Jewett, J. C., Orchowski, M., Glueck, D. S., Sommer, R. D., Lam, K., Incarvito, C. D., Concolino, T. E., Ceccarelli, C., Zakharov, L. N., & Rheingold, A. L. (2003). Palladium-catalyzed asymmetric phosphination. Enantioselective synthesis of PAMP-BH3, ligand effects on catalysis, and direct observation of the stereochemistry of transmetalation and reductive elimination. Organometallics, 22(16), 3205-3221.
Abstract:
The complexes Pd(diphos)(o-An)(I) (o-An = o-MeOC6H4; diphos = dppe (3), (S,S)-Chiraphos (4), (R,R)-Me-Duphos (5), (R,S) -t-Bu-Josiphos (6), (R)-Tol-Binap (7)) were prepared. Complex 6 catalyzed the coupling of PH(Me)(Ph)(BH3) (2) with o-AnI in the presence of base to yield PAMP-BH3 (P(Me)(Ph)(o-An)(BH3) (1)) in low enantiomeric excess. The course of stoichiometric reactions of 3-7 with 2 and NaOSiMe3 depended on the diphosphine ligand. Complexes 6 and 7 gave PAMP-BH3 (1) and Pd(0) species; no intermediates were observed. With 3, the intermediate Pd(dppe)(o-An)(P(Me)(Ph)(BH3)) (10) was observed by 31P NMR, while 4 gave the isolable diastereomeric palladium complexes (Sp)-Pd((S,S)-Chiraphos)(o-An)(P(Me)(Ph)(BH3)) (11a) and (RP)-Pd((S,S)-Chiraphos)(o-An)(P(Me)(Ph)(BH3)) (11b), whose absolute configurations were determined by X-ray crystallography after separation. The analogous Pd((R,R)-Me-Duphos)(o-An)(P(Me)(Ph)(BH3)) diastereomers (12a,b) were also separated and isolated. Treatment of 4 with highly enantioenriched 2 (R or S) gave 11a or 11b in high diastereomeric excess with retention of configuration at phosphorus. P-C reductive elimination from either isomer of highly diastereoenriched 11 in the presence of excess diphenylacetylene yielded Pd((S,S)-Chiraphos)(PhC≡CPh) (14) and highly enantioenriched PAMP-BH3 (1), with retention of configuration.
Dang, Y., Schneider-Poetsch, T., Eyler, D. E., Jewett, J. C., Bhat, S., Rawal, V. H., Green, R., & Liu, J. O. (2011). Inhibition of eukaryotic translation elongation by the antitumor natural product Mycalamide B. RNA, 17(8), 1578-1588.
PMID: 21693620;PMCID: PMC3153980;Abstract:
Mycalamide B (MycB) is a marine sponge-derived natural product with potent antitumor activity. Although it has been shown to inhibit protein synthesis, the molecular mechanism of action by MycB remains incompletely understood. We verified the inhibition of translation elongation by in vitro HCV IRES dual luciferase assays, ribosome assembly, and in vivo [ 35S]methinione labeling experiments. Similar to cycloheximide (CHX), MycB inhibits translation elongation through blockade of eEF2-mediated translocation without affecting the eEF1A-mediated loading of tRNA onto the ribosome, AUG recognition, or dipeptide synthesis. Using chemical footprinting, we identified the MycB binding site proximal to the C3993 28S rRNA residue on the large ribosomal subunit. However, there are also subtle, but significant differences in the detailed mechanisms of action of MycB and CHX. First, MycB arrests the ribosome on the mRNA one codon ahead of CHX. Second, MycB specifically blocked tRNA binding to the E-site of the large ribosomal subunit. Moreover, they display different polysome profiles in vivo. Together, these observations shed new light on the mechanism of inhibition of translation elongation by MycB. Published by Cold Spring Harbor Laboratory Press. Copyright © 2011 RNA Society.
Knyazeva, D. C., Kimani, F. W., Blanche, J., & Jewett, J. C. (2017). Hexyl triazabutadiene as a potent alkylating agent. TETRAHEDRON LETTERS, 58(28), 2700-2702.
